PubMed Health⌕ Search

Biomedical subjects

Chung-Cheng Hsieh

Publications and source records attributed to Chung-Cheng Hsieh.

At least 19 recordsLinked to original sources

Patterns of serum type 1 and type 2 immune markers in healthy carriers of HTLV-I.

Type 1 immunity appears to be diminished in healthy Japanese carriers of human T-lymphotropic virus type I (HTLV-I), but type 2 status remains undetermined. To further examine the subclinical effect of HTLV-I on host immunity, we measured serum antibodies to the Epstein-Barr virus (EBV) in 415 healthy Japanese adults to broadly characterize type 1 status. Levels of the type 2 biomarkers total immunoglobulin E (IgE), soluble CD23 (sCD23), and soluble CD30 (sCD30) were assessed in 167, 142, and 135 of these subjects, respectively. We analyzed the association of HTLV-I with levels of each serum marker using linear and logistic regression. Altered EBV antibody profiles that are consistent with deficient type 1 immunity were more prevalent in HTLV-I carriers than non-carriers (odds ratio (OR) = 2.8, 95% confidence interval (CI) = 1.5-5.3). Carriers also had 45% lower total IgE levels (P = 0.04) than non-carriers. In contrast, HTLV-I infection was not significantly associated with elevated levels of sCD23 or sCD30. These observations are contrary to our expectation of elevated type 2 biomarkers among carriers. We conclude that in this population, healthy carriers of HTLV-I may have subclinical deficiencies in both type 1 and type 2 immunity, and that type 1 and type 2 immunity are not necessarily reciprocal in persons with subclinical immune dysregulation.

Adult↗

Adhesion receptor expression by CD34+ cells from peripheral blood or bone marrow grafts: correlation with time to engraftment.

OBJECTIVE: This study was undertaken to define the pattern of cell adhesion receptor expression by the CD34+ progenitor cells from mobilized peripheral blood and bone marrow from normal and autologous donors, and to correlate the adhesion receptor profile with time to blood cell recovery for patients undergoing autologous transplant. METHODS: Blood cell recovery was determined by absolute neutrophil count (> 500/microL), time to last red cell transfusion, and platelet count (> 50,000/microL and > 100,000/microL). The analysis for expression of adhesion receptors alphaL (CD11a), alpha2 (CD49b), alpha3 (CD49c), alpha4 (CD49d), alpha5 (CD49e), alpha6 (CD49f), beta1 (CD29), L-selectin (CD62L), ICAM-1 (CD54), PECAM-1 (CD31), HCAM (CD44), and P-selectin (CD62P) was performed by two-color flow cytometry. The Kruskal-Wallis test and Spearman's rank correlation were used for statistical analysis. RESULTS: Statistical analysis of adhesion expression by the CD34+ population for patients undergoing autologous transplant demonstrated that the higher percent expression of PECAM-1 correlated with longer time to platelet recovery (> 100,000/microL, p = 0.049). In contrast, the higher the percent expression of alpha6 (p = 0.013) and the increased density of expression of alpha2 (p = 0.035), alpha3 (p = 0.023), alpha4 (p = 0.044), beta1 (p = 0.027), and ICAM-1 (p = 0.010) correlated with shorter time to platelet recovery. Neutrophil recovery time decreased with increased density of expression of alphaL (p = 0.014) and P-selectin (p = 0.007) receptors. Increased density of expression of CD44 (HCAM) was associated with longer time to red blood cell recovery (p = 0.05). CONCLUSION: These data suggest that upregulation of specific adhesion receptors or selection of certain cell populations could result in earlier blood cell recovery after transplant.

Adult↗

Analysis of RNA-binding protein IMP3 to predict metastasis and prognosis of renal-cell carcinoma: a retrospective study.

BACKGROUND: Distant metastasis is the main cause of death from renal-cell carcinoma, and the metastatic potential of tumours is often unpredictable. We aimed to investigate whether IMP3, an oncofetal RNA-binding protein, can be used as a biomarker to predict metastasis and prognosis of renal-cell carcinoma. METHODS: We studied 501 primary and metastatic renal-cell tumours. 371 patients with localised primary tumours were further investigated by use of survival analysis. We assessed IMP3 expression in tumour tissues by immunohistochemistry, and IMP3 mRNA and protein expression in selected tissues by quantitative real-time PCR and western blot analysis. FINDINGS: Compared with non-metastatic renal-cell tumours, IMP3 expression was greatly increased not only in metastatic tumours but also in a subset of primary tumours that were likely to subsequently develop metastases. Patients with primary localised tumours that did not express IMP3 had a longer metastasis-free survival and overall survival than did those with tumours expressing IMP3 (p<0.0001). Patients with IMP3-positive localised tumours had a much lower 5-year metastasis-free survival than did those with IMP3-negative tumours (for stage I tumours, 44% vs 98%, hazard ratio 17.18 [95% CI 7.82-37.78]; stage II, 41% vs 94%, 10.14 [3.46-29.68]; stage III, 16% vs 62%, 4.04 [2.23-7.31]). IMP3 expression was also associated with reduced 5-year overall survival (stage I, 32% vs 89%, 6.44 [3.63-11.42]; stage II, 41% vs 88%, 6.93 [2.63-18.27]; stage III, 14% vs 58%, 3.46 [1.98-6.05]). Multivariable analysis of IMP3 status (positive vs negative) in primary tumours showed hazard ratios of 5.84 (95% CI 3.60-9.49) for metastasis-free survival and 4.01 (2.66-6.05) for overall survival (both p<0.0001), which were much higher than hazard ratios associated with other independent risk factors. INTERPRETATION: IMP3 is an independent prognostic marker that can be used at initial diagnosis of renal-cell carcinoma to identify patients who have a high potential to develop metastasis and who might benefit from early systemic treatment.

Adult↗

Diet during pregnancy and levels of maternal pregnancy hormones in relation to the risk of breast cancer in the offspring.

Birth weight is positively associated with the risk of breast cancer in the offspring and the underlying process is likely to involve the pregnancy endocrine milieu. We have examined the association of diet and related factors during pregnancy with the levels (at the 16th and 27th gestational week) of maternal pregnancy oestradiol, oestriol, sex hormone-binding globulin (SHBG), progesterone and prolactin, in a cohort of 270 Caucasian women who delivered in a major hospital in Boston, USA. Oestradiol and oestriol were not strongly associated with any of the diet-related variables, but SHBG was significantly and consistently related inversely to pre-pregnancy body mass index and weight gain during pregnancy, and positively to vegetable and pulses intake. Pregnancy progesterone was associated positively with alcohol and inversely with polyunsaturated lipid and vitamin B12 intake, whereas pregnancy prolactin was inversely associated with cereal consumption. If the pregnancy hormones studied are indeed involved in the intra-uterine origin of breast cancer, these findings, if confirmed, would focus dietary advice to pregnant women, with a view to reducing the risk of breast cancer in the offspring, towards avoidance of excess energy intake and an emphasis on plant foods. This advice does not contradict current dietary advice on prudent diet during pregnancy and throughout life.

Adult↗

Reproducibility of assays for steroid hormones, prolactin and insulin-like growth factor-1 in umbilical cord blood.

We assessed the reproducibility of measurements of plasma hormone and binding protein levels in umbilical cord blood collected from 30 male and female babies. They were delivered as singleton births from full-term pregnancies (gestational age >or= 37 weeks) in a cord blood donation programme. We assayed three plasma replicates from each cord blood sample at two points in time. Plasma oestradiol, unconjugated oestriol, testosterone, progesterone, prolactin, sex-hormone binding globulin (SHBG), insulin-like growth factor-1 (IGF-1), and IGF binding protein-3 (IGFBP-3) levels were measured in duplicates in the same batch (batch 1). In addition, another set of assays was conducted for each cord blood 1 year apart in a different batch (batch 2). Means and standard deviations for each hormone and binding protein were similar in replicates assayed in batch 1 and 2. Pearson's correlation coefficients were 0.9 or higher in duplicates assayed in batch 1. The correlation coefficients were between 0.77 and 0.96 for between-batch assays. Intra-class correlation coefficients (ICC) were higher than 0.9 for assay of SHBG [95% CI 0.92, 1.0] and progesterone [95% CI 0.87, 0.97] and between 0.8 and 0.9 for assay of oestradiol, unconjugated oestriol, prolactin, IGF-1, and IGFBP-3. The lowest ICC value was found for testosterone (ICC = 0.74; [95% CI 0.56, 1.0]). These data indicate a high reproducibility of cord blood hormone measurements; minimal differences were observed between the calibrated and the original regression coefficients for the association of hormones/binding proteins with percent of CD34+ cells in mononuclear cells.

Carrier Proteins↗

A prospective study of the transient decrease in ovarian cancer risk following childbirth.

Epidemiologic evidence shows that the risk of ovarian cancer is decreased following childbirth. We examined the time points when the decreased risk of postpartum maternal ovarian cancer reaches the lowest point and whether the protective effect diminishes over time. A case-control study nested within the Swedish Fertility Register included 10,086 cases of epithelial ovarian cancer recorded in the Swedish Cancer Register from 1961 to 2001. From the Fertility Register, 49,249 eligible subjects matched to the cases by age were selected as controls. The analysis contrasted risk between adjacent parities through logistic regression models that included indicator variables representing each year of age, age at delivery, and time since delivery. Compared with nulliparous women, uniparous women had a transient decrease in maternal ovarian cancer risk at 2 years after delivery (spline-derived odds ratio, 0.71; 95% confidence interval, 0.53-0.95, for those delivered at age 25 years) and maintained a lower risk for 4 years postpartum. Similar transient decreases were observed in biparous women compared with uniparous women and in women with three parities compared with biparous women. The protective effect of childbearing seemed to diminish with time. The transient decrease in postpartum ovarian cancer risk may define the latent period required for pregnancy hormones in clearing out ovarian cells that have undergone early stages of malignant transformation. The period before the risk increases again could indicate the period required for ovarian cancer induction.

Adolescent↗

Maternal height, pregnancy estriol and birth weight in reference to breast cancer risk in Boston and Shanghai.

Birth weight has been positively associated with breast cancer risk in adult life and is positively associated with the principal pregnancy estrogen estriol. Birth weight is lower among Chinese women than among Caucasian women, but paradoxically, pregnancy estriol levels are higher among the former than the latter. We studied a cohort of 317 Caucasian pregnant women in Boston, MA, and 339 Chinese pregnant women in Shanghai, China. We investigated whether maternal height, which is inversely associated with pregnancy estriol levels, interacts with this hormone in relation to birth weight, thus accommodating the apparently contradictory ecologic and analytic evidence concerning the role of pregnancy estrogens on breast cancer risk in the offspring. In both Boston and Shanghai, there was a positive association of pregnancy estriol with birth weight among taller women, whereas among shorter women the association was essentially null. The relevant interaction terms were highly significant in Boston (p approximately 0.006), whereas in Shanghai, where pregnant women were generally shorter, the interaction term was suggestive (p approximately 0.14). We conclude that maternal height should be considered an important risk factor for breast cancer in the offspring since it is a crucial determinant of birth weight, both directly and through positive interaction with the principal pregnancy estrogen estriol.

Birth Weight↗

The clonal expansion of human T lymphotropic virus type 1-infected T cells: a comparison between seroconverters and long-term carriers.

BACKGROUND: The clonal expansion of human T lymphotropic virus type 1 (HTLV-1)-infected T cells is considered to be important for the maintenance of infection. However, the process by which the clonality of HTLV-1-infected T cells is established is not understood. METHODS: HTLV-1 clonality in 4 adult seroconverters was analyzed by inverse long polymerase chain reaction (PCR) followed by cloning of the PCR products and evaluation of restriction fragment-length polymorphism. The results were compared with those for 8 long-term HTLV-1 carriers. RESULTS: The clonality of HTLV-1-infected T cells in the seroconverters arose stochastically and was variable 3-5 years after seroconversion. On the basis of the frequency with which clones of cells infected with unique HTLV-1 provirus integration sites appeared, it was clear that the seroconverters had a greater number of unique clones with fewer infected cells than did the long-term carriers. CONCLUSIONS: The clonality of the HTLV-1-infected T cells in the adult seroconverters, who had been newly infected via HTLV-1-carrier spouses, was more heterogeneous and less stable than that of the HTLV-1-infected T cells in long-term carriers, who were more likely to have been infected during infancy. The mechanism for the selective maintenance of certain clones in asymptomatic HTLV-1 carriers likely plays a role in the initiation of leukemogenesis.

Aged↗

Association of fetal hormone levels with stem cell potential: evidence for early life roots of human cancer.

Intrauterine and perinatal factors have been linked to risk of childhood leukemia, testicular cancer, and breast cancer in the offspring. The pool of stem cells in target tissue has been suggested as a critical factor linking early life exposures to cancer. We examined the relation between intrauterine hormone levels and measurements of stem cell potential in umbilical cord blood. Cord blood donors were 40 women, ages >/=18 years, who delivered, from August 2002 to June 2003, a singleton birth after a gestation of at least 37 weeks. We assayed plasma concentrations of estradiol, unconjugated estriol, testosterone, progesterone, prolactin, sex hormone binding globulin, insulin-like growth factor-I (IGF-I), and IGF binding protein-3. For stem cell potential, we measured concentrations of CD34(+) and CD34(+)CD38(-) cells and granulocyte-macrophage colony-forming unit (CFU-GM). We applied linear regression analysis and controlled for maternal and neonatal characteristics. We found strong positive associations between IGF-I and stem cell measures, 1 SD increase in IGF-I being associated with a 41% increase in CD34(+) (P = 0.008), a 109% increase in CD34(+)CD38(-) (P = 0.005), and a 94% increase in CFU-GM (P = 0.01). Similar associations were observed for IGF binding protein-3. Among steroid hormones, estriol and testosterone were significantly positively associated with CD34(+) and CFU-GM. These findings indicate that levels of growth factors and hormones are strongly associated with stem cell potential in human umbilical cord blood and point to a potential mechanism that may mediate the relationship between in utero exposure to hormones and cancer risk in the offspring.

Antigens, CD↗

Longitudinal trends of stomach cancer and esophageal cancer in Yangzhong County: a high-incidence rural area of China.

OBJECTIVE: This study aims to investigate the recent trends in incidence rates of stomach cancer and esophageal cancer in a high-incidence rural area of China. METHODS: All new cancer occurrences registered between 1991 and 2003 in the Yangzhong Cancer Registry were reviewed. Yearly age-specific and age-adjusted incidence rates were calculated for males and for females. Longitudinal trends of cancer incidence were estimated by the estimated annual percentage change method. RESULTS: In total 12 691 incident cancer cases were registered, with 7159 males (56.41%) and 5532 females (43.59%). Adjusting to the world standard population, the incidence rate of all cancers decreased significantly across the period 1991-2003 from 357.02 to 283.21 per 10 person-years. For males this rate decreased from 447.22 to 346.72 per 10 person-years, and for females the incidence rate decreased from 284.36 to 225.73 per 10 person-years. The major cancers in Yangzhong County were stomach cancer and esophageal cancer, accounting for more than 70% of all cancer occurrences. During the past 13 years, the incidence rates of stomach cancer decreased greatly from 231.92 to 145.26 per 10 person-years in males and from 114.16 to 74.59 per 10 person-years in females. The estimated annual percentage changes of stomach cancer incidence were -2.96% [95% confidence interval (CI), -2.99% to -2.92%] in males and -2.86% (95% CI, -2.89% to -2.82%) in females. Incidence rates for esophageal cancer decreased slightly from 121.48 to 93.84 per 10 person-years in males with an estimated annual percentage change of -1.39% (95% CI, -1.42% to -1.36%), and from 99.74 to 73.73 per 10 person-years in females at an annual change of -2.18% (95% CI, -2.22% to -2.14%). CONCLUSION: Findings from this study showed that, although there is a decreasing trend of stomach cancer and esophageal cancer in this high-incidence area, the rates remain high. Future effort should be directed toward identifying factors behind the high rates and those contributing to the decreasing trend.

Adult↗

Breast cancer incidence in women prenatally exposed to maternal cigarette smoke.

BACKGROUND: Clinical studies show that maternal cigarette smoking reduces pregnancy estrogen levels. Women prenatally exposed to maternal cigarette smoke may, therefore, have a lower breast cancer risk because the fetal mammary gland's exposure to maternal estrogen is decreased. Associations between prenatal maternal cigarette smoke exposure and breast cancer, however, have not been observed in previous case-control studies that relied on exposure assessment after the onset of cancer. At the start of this study, cigarette smoking history was obtained directly from the mother. METHODS: The National Cooperative DES Adenosis project was a follow-up study of health outcomes in women prenatally exposed to diethylstilbestrol (DES). At the start of the study, women's mothers provided information about cigarette smoking habits during the time they were pregnant with the study participant. In the current study, the breast cancer rates are compared among 4031 women who were or were not prenatally exposed to maternal cigarette smoke. The resultant relative rate (RR) is adjusted for potential confounding by other breast cancer risk factors using Poisson regression modeling. RESULTS: Fetal exposure to maternal cigarette smoke appeared to be inversely associated with breast cancer incidence (RR = 0.49; 95% confidence interval [CI] = 0.24-1.03). The inverse association was more apparent among women whose mothers smoked 15 cigarettes or fewer per day than among daughters of heavier smokers. There were, however, too few cases to precisely estimate a possible dose-response relationship. CONCLUSION: These results support the hypothesis that in utero exposure to maternal cigarette smoke reduces breast cancer incidence.

Adult↗

Physical activity as a determinant of mortality in women.

BACKGROUND: There is substantial evidence that higher levels of activity reduce the risk of mortality, but several research questions remain about the protective effect of physical activity. We aimed to quantify the effect of physical activity on overall mortality in younger women and to assess the effect of past versus current activity. METHODS: During 1991-1992, we enrolled 99,099 women, age 30-49 years, from the entire country of Norway and one Swedish region, in a population-based cohort study. The women provided information on physical activity level at age 14 and 30 years and at enrollment, as well as information on other personal characteristics at enrollment. We achieved complete follow-up into 2003 using record linkages to nationwide registers. We used Cox proportional hazard models to calculate multivariate relative risks (RRs) of dying from any cause. RESULTS: During an average 11.4 years of follow-up, 1,313 women died. Risk of death decreased with increasing physical activity at enrollment (5 categories; P for trend<0.0001) and was reduced by half in the highest compared with the lowest category (RR=0.46; 95% confidence intervals=0.33-0.65). This protective effect was consistent across strata of age at entry, smoking, country, and education. After adjustment for physical activity at enrollment, activity at age 14 and 30 was not associated with mortality. CONCLUSIONS: Current physical activity substantially reduces mortality among women. This association is observed even with low levels of physical activity and is accentuated with increased physical activity.

Adult↗

Pregnancy hormone concentrations across ethnic groups: implications for later cancer risk.

A variety of in utero factors have been associated with risk of adult cancers, particularly birth weight, toxemia, and gestational age. These factors are thought to reflect hormonal exposures during pregnancy. We hypothesized that the prenatal hormonal milieu may explain part of the variation in cancer rates across ethnic groups, for example, the higher incidence of breast cancer in the Caucasian compared with Hispanic women and the higher incidence of prostate and lower incidence of testicular cancers among African-Americans compared with Caucasians. We measured hormones in early pregnancy blood samples from three ethnic groups in a health care plan in Boston, MA. Mean levels of androstenedione, testosterone, estrone, and prolactin were significantly lower in Caucasian women compared with Hispanic women. Although not statistically significant, estradiol levels were lower in Caucasian compared with Hispanic or African-American women. Concentrations of androstenedione, testosterone, and progesterone were notably higher in African-American compared with Caucasian or Hispanic women. These data are consistent with hypotheses that in utero hormonal exposures may explain some of the ethnic group differences in cancer risk.

Adult↗

Maternal breast cancer risk after the death of a child.

The possible association between a severe traumatic life event (death of a child) and breast cancer risk was examined in a case-control study nested within a nation-wide cohort in Sweden. Our study population included 27,571 women with breast cancer and 141,798 control women born between 1925-1976. After adjustment for age, parity, age at first birth and education, the overall risk estimate for breast cancer among all women that had experienced the death of a child was 1.05 (95% confidence interval [CI] = 0.96-1.15). Among uniparous women the corresponding odds ratio (OR) was 1.27 (95% CI = 0.98-1.64). When stratifying for child's age at death a significant risk increase was detected among women that had lost their only child when the child was between 1-4 years of age (OR = 2.65; 95% CI = 1.06-6.60). These findings do not support an overall increase in breast cancer risk after the death of a child, a severe traumatic life event. Based on a small number of subjects, our finding of an increased risk in a subgroup of uniparous women losing their only child could be due to chance.

Adolescent↗

Micronutrient intake during pregnancy in relation to birth size.

BACKGROUND: There exists very little information on possible effects on birth size of micronutrient intakes at levels that are usually encountered among pregnant women in developed countries. AIM OF THE STUDY: To examine the relation of the intake of 20 micronutrients with birth weight, placental weight, birth length and head circumference of the offspring. METHODS: In a cohort of 222 Caucasian women with singleton pregnancies in Boston, USA, diet during pregnancy was ascertained at the 27th gestational week through a validated semi-quantitative food frequency questionnaire, covering also intake of dietary supplements. Micronutrient intakes were correlated with birth size parameters after adjustment for confounding variables, including total energy intake. RESULTS: Pantothenic acid, sodium and vitamin E were positively associated with all four birth size parameters. For pantothenic acid the association was statistically significant with respect to birth length, whereas for sodium with respect to head circumference and for vitamin E with respect to birth weight. In contrast, zinc was inversely associated with all four birth size parameters and the association was statistically significant with respect to head circumference. CONCLUSIONS: In a moderately sized prospective study, we found evidence that pregnancy intake of pantothenic acid, vitamin E and sodium may be positively related with at least one of the studied birth size parameters, whereas an inverse association was found with respect to zinc intake. For the remaining 16 micronutrients, our findings indicate that they are not associated with birth size, at least within the range of intake encountered in this investigation. The results of this exploratory analysis need to be confirmed before pathophysiologic interpretations and generalizations are attempted.

Adolescent↗

Circadian variations of bone marrow engraftability.

Circadian rhythms exist for hematopoiesis, but little is known about circadian variation of bone marrow engraftability and host "acceptability". Using a B6.SJL to C57BL/6J congenic transplant model, we chose 3-times with light on: Hours After Light Onset (HALO) 4, 8, and 12 and 3-times with light off: HALO 16, 20, and 24. The mice were conditioned on a 12-h light/dark cycles. Recipient mice (100 cGy) received 40 million cells. We demonstrated a significant variation of bone marrow engraftability into bone marrow, spleen, and thymus when donor animals were subjected to changes in their light/dark cycles. Two statistically significant nadirs in all three organs were observed at HALO 8 and 24 in experiments carried out in July, while an identical set of experiments in February analyzing engraftment in marrow and spleen showed nadirs at HALO 8, but not at HALO 24. Marrow progenitors from the July experiments showed nadirs at HALO 12 and 24. The percentage of progenitors in S phase peaked at HALO 8 and 24. Interestingly, there were no changes in the ability of host to accept grafts with changes in the light/dark cycles of host animals. Circadian variations of bone marrow engraftability are important and should be considered in bone marrow transplant strategies.

Animals↗

Stem cells and prenatal origin of breast cancer.

The hypothesis that in utero exposure to pregnancy hormones, notably estrogens, is related to the occurrence of breast cancer in the offspring has been examined in a number of epidemiological and experimental studies. Many studies have provided direct or indirect evidence that supports the hypothesis of an intrauterine component in the origin of breast cancer. Human studies to examine the underlying biological mechanisms, however, have been limited. We review the likely role of stem cells in hormone-mediated carcinogenic process, particularly as intermediate steps between in utero exposure to hormones and breast cancer. We summarize also studies related to the assumptions of the hypothesis concerning in utero exposure. We propose the use of stem cell potential as a measurable variable of the 'fertile soil', a term that has been used to characterize the consequences of fetal exposure to intrauterine environment. We conclude by outlining a feasible population-based study that measures stem cell potential to explore mechanisms mediating the relation between in utero exposure to pregnancy hormones and breast cancer risk in the offspring.

Breast Neoplasms↗